Production of growth promoting substances



Patented Feb. 3, 1942 PRODUCTION OFGROWTH'PROMOTING A SUB$TANCES Herschel K. Mitchell, Austin, .Tex.,' assignorto Research Corporation, New York, N. Y., a corporation of New'York No Drawing. Application March .25, 1940, Serial No. 325,839

6 Claims.

' This invention relates to the production of substances useful for the growth of plants and micro-organism and believed to be necessary for the proper nutrition of animals. Pantothenic acid, a substance which promotes the growth of diverse organisms is believed to have a structure corresponding to the following formula:

CH3 CHzHlCHOH-C0 NHCHrCHzCO0H However, I have found that certain compounds with the same skeleton structure but. containing more hydroxyl groups, are also valuable as growth promoting agents and function similarly to the synthetic pantothenic acid formulated above.

As an example of the production and use of such a growth promoting substance I cite the following experiments. a

Twenty grams of propionaldehyde were added dropwise to a cooled mixture of 55 grams of 38% formaldehyde and 30 grams of potassium carbonate. After three days shaking the solution was extracted repeatedly with ether. The sixteen grams of viscous aldehyde obtained was dissolved in 20 ml. of ether followed by addition of ml. of liquid hydrogen cyanide and one drop of triethyl amine all in an ice bath. After standing over night the mixture was treated with 50 ml. of 6 N hydrochloric acid on the. steam bath for four hours. The material was then made strongly alkaline with sodium hydroxide, then extracted twice with ether and the extract discarded. The water solution was made to pH L with concentratedhydrochloric acid and heated on the steam bath for five hours. The resulting product was extracted twice with ether discarding the extract which contained very little lactone. The solution was then extracted continuously for 24 hours with ether. Evaporation of the ether gave a viscous liquid soluble in water and alcohol. Heating the crude lactone with 0.05

N sodium hydroxide showed it to be at least 95% lactone and to have a saponification equivalent of 143. The theoretical forthe compound A sample of this lactone (2.8 mgs.) was heated with 10 mgs. of p alanine methyl esterat 70 C. for one hour. The resulting product was treated with 0.1 ml. of 1 N potassium hydroxide in absolute methanol to remove the ester group and give the compound in racemic' form:

The growth promoting activity of this produc was shown by the fact that in three tests the reaction product from 0.5 gamma, 1.0 gamma and-3 gamma of-lactone yielded 03,08, and 1.5 mg. units (Weinstock, Mitchell, Pratt and Williams Joum. Am. Chem. Soc. 61, 1421, 1939) of pantothenic acid activity as measured by a modification of the L. casei test of Snell, Peterson and Strong. Joum. Am. Chem. Soc. 60, 2825 (1938) Control tests in which ,3 alanine ester alone was used, gave no growth stimulation.

The a hydroxy 'y lactone with two otherfree hydroxyl groups, viz. 0

0111021 on. encer-0:0

dehyde and formaldehyde followed by cyanohydrin synthesis and hydrolysis as described above. This when condensed with p alanine ester and subsequently hydrolyzed yields the product:

cmoH omonc-cnonoonncrncmcoon The above are cited as examples only and the invention is not limited to .the specific cases cited.

I claim:

1. A growthpromoting substance having th structure represented by the formula:

ornori' CHzOH-('JGHOHCO-NH-CHzCHzCOOH 7 i a 2. A process of producing a growth promoting substance by condensing the lactone 0H,- -CHOHC=O with betaalanine esterand subsequent hydrolysis of the ester linkage.

ing substance by condensing the Iactone:

4. A DIOCESS Of producing a. growth promot- 6 The pro cess comprises reacting a fl-alanine ester with a. lactone of the group havcmoH 10 ing the formulae: our -CHOHC=O v v 0111011 I 11,011 cm .CHOHC=O 0 v H: with a beta-alanine ester and hydrolysing the 15 9 ester linkage. and

5. The process which comprises reacting a.

OH OH ,S-alanine ester with a lactone of the group hava ing the formulae; CHH O=O CH: cHOH-c= 0 O H and subsequently cleaving the ester linkage by O hydrolysis.

HERSCHEL K. MITCHELL. 

